The aim of this proposed program project is to apply cell and molecular biological techniques to the study of (I) basement membrane and vascular endothelial cell alterations in diabetes, (II) the determinants of mesangial cell proliferation and matrix accumulation in chronic glomerulosclerosis and (III) the regulation of membrane and cytoskeletal organization in renal epithelial cell injury and regeneration. Each of these areas will be investigated using in vitro cell culture models to study cell matrix interactions, cytoskeletal function and factors which modulate proliferation, organization and differentiation of cell structure and function. Drs. Furthmayr, Madri and Benz will aim to elucidate the chemical changes that occur in basement membrane proteins in diabetes and to understand the functional significance of these modifications on microvascular endothelial cells. Drs. Sterzel, Foellmer and Kashgarian proposed to characterize the determinants of mesangial growth and to elucidate the interactions of mesangial cells, matrix components and growth factors and to investigate the role that these factors may play in the glomerulosclerosis that occurs in progressive renal disease. Drs. Morrow, Mooseker, Benz and Kashgarian propose to examine the regulation of membrane and cytoskeletal organization in renal epithelial cells to elucidate the post-translational factors affecting the establishment and maintenance of cell polarity and differentiation in renal cell injury, regeneration and adaptation. The results generated by this research are expected to help define the cellular mechanisms involved in the initiation and perpetuation of pathologic processes that lead to chronic renal failure.